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Ragulator and GATOR1 complexes promote fission yeast growth by attenuating TOR complex 1 through Rag GTPases
TOR complex 1 (TORC1) is an evolutionarily conserved protein kinase complex that promotes cellular macromolecular synthesis and suppresses autophagy. Amino-acid-induced activation of mammalian TORC1 is initiated by its recruitment to the RagA/B-RagC/D GTPase heterodimer, which is anchored to lysosom...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5752196/ https://www.ncbi.nlm.nih.gov/pubmed/29199950 http://dx.doi.org/10.7554/eLife.30880 |
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author | Chia, Kim Hou Fukuda, Tomoyuki Sofyantoro, Fajar Matsuda, Takato Amai, Takamitsu Shiozaki, Kazuhiro |
author_facet | Chia, Kim Hou Fukuda, Tomoyuki Sofyantoro, Fajar Matsuda, Takato Amai, Takamitsu Shiozaki, Kazuhiro |
author_sort | Chia, Kim Hou |
collection | PubMed |
description | TOR complex 1 (TORC1) is an evolutionarily conserved protein kinase complex that promotes cellular macromolecular synthesis and suppresses autophagy. Amino-acid-induced activation of mammalian TORC1 is initiated by its recruitment to the RagA/B-RagC/D GTPase heterodimer, which is anchored to lysosomal membranes through the Ragulator complex. We have identified in the model organism Schizosaccharomyces pombe a Ragulator-like complex that tethers the Gtr1-Gtr2 Rag heterodimer to the membranes of vacuoles, the lysosome equivalent in yeasts. Unexpectedly, the Ragulator-Rag complex is not required for the vacuolar targeting of TORC1, but the complex plays a crucial role in attenuating TORC1 activity independently of the Tsc1-Tsc2 complex, a known negative regulator of TORC1 signaling. The GATOR1 complex, which functions as Gtr1 GAP, is essential for the TORC1 attenuation by the Ragulator-Rag complex, suggesting that Gtr1(GDP)-Gtr2 on vacuolar membranes moderates TORC1 signaling for optimal cellular response to nutrients. |
format | Online Article Text |
id | pubmed-5752196 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-57521962018-01-04 Ragulator and GATOR1 complexes promote fission yeast growth by attenuating TOR complex 1 through Rag GTPases Chia, Kim Hou Fukuda, Tomoyuki Sofyantoro, Fajar Matsuda, Takato Amai, Takamitsu Shiozaki, Kazuhiro eLife Cell Biology TOR complex 1 (TORC1) is an evolutionarily conserved protein kinase complex that promotes cellular macromolecular synthesis and suppresses autophagy. Amino-acid-induced activation of mammalian TORC1 is initiated by its recruitment to the RagA/B-RagC/D GTPase heterodimer, which is anchored to lysosomal membranes through the Ragulator complex. We have identified in the model organism Schizosaccharomyces pombe a Ragulator-like complex that tethers the Gtr1-Gtr2 Rag heterodimer to the membranes of vacuoles, the lysosome equivalent in yeasts. Unexpectedly, the Ragulator-Rag complex is not required for the vacuolar targeting of TORC1, but the complex plays a crucial role in attenuating TORC1 activity independently of the Tsc1-Tsc2 complex, a known negative regulator of TORC1 signaling. The GATOR1 complex, which functions as Gtr1 GAP, is essential for the TORC1 attenuation by the Ragulator-Rag complex, suggesting that Gtr1(GDP)-Gtr2 on vacuolar membranes moderates TORC1 signaling for optimal cellular response to nutrients. eLife Sciences Publications, Ltd 2017-12-04 /pmc/articles/PMC5752196/ /pubmed/29199950 http://dx.doi.org/10.7554/eLife.30880 Text en © 2017, Chia et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Cell Biology Chia, Kim Hou Fukuda, Tomoyuki Sofyantoro, Fajar Matsuda, Takato Amai, Takamitsu Shiozaki, Kazuhiro Ragulator and GATOR1 complexes promote fission yeast growth by attenuating TOR complex 1 through Rag GTPases |
title | Ragulator and GATOR1 complexes promote fission yeast growth by attenuating TOR complex 1 through Rag GTPases |
title_full | Ragulator and GATOR1 complexes promote fission yeast growth by attenuating TOR complex 1 through Rag GTPases |
title_fullStr | Ragulator and GATOR1 complexes promote fission yeast growth by attenuating TOR complex 1 through Rag GTPases |
title_full_unstemmed | Ragulator and GATOR1 complexes promote fission yeast growth by attenuating TOR complex 1 through Rag GTPases |
title_short | Ragulator and GATOR1 complexes promote fission yeast growth by attenuating TOR complex 1 through Rag GTPases |
title_sort | ragulator and gator1 complexes promote fission yeast growth by attenuating tor complex 1 through rag gtpases |
topic | Cell Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5752196/ https://www.ncbi.nlm.nih.gov/pubmed/29199950 http://dx.doi.org/10.7554/eLife.30880 |
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